Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought?
Abstract
Osteoarthritis (OA) of the hip and knee is among the most common joint disorders. Intra-articular corticosteroid (IACS) injections are frequently performed to treat OA and other joint-related pain syndromes; however, there is conflicting evidence on their potential benefit. There is a lack of prospective and large retrospective studies evaluating potential joint findings, including increased risk for accelerated OA progression or adverse joint events, after treatment with IACS injection. Four main adverse joint findings have been structurally observed in patients after IACS injections: accelerated OA progression, subchondral insufficiency fracture, complications of osteonecrosis, and rapid joint destruction, including bone loss. Physicians, including radiologists, should be familiar with imaging findings and patient characteristics that may help them identify potential joints at risk for such events. The purpose of this report is to review the existing literature, describe observed adverse joint events after IACS injections, and provide an outlook on how this may affect clinical practice. Additional research endeavors are urgently needed to better understand and identify risk factors prior to intervention and to detect adverse joint events after injection as early as possible to prevent or minimize complications.
© RSNA, 2019
See also the editorial by Kijowski in this issue.
Summary
An increased clinical awareness of adverse joint events after intra-articular corticosteroid injections has led to potential imaging findings and patient characteristics that may assist in identifying which joints could be at risk, although high-quality evidence regarding this topic is lacking.
Essentials
■ Adverse joint events after intra-articular corticosteroid (IACS) injection, including accelerated osteoarthritis progression, subchondral insufficiency fracture, complications of osteonecrosis, and rapid joint destruction with bone loss, are becoming more recognized by physicians, including radiologists, who may consider adding these risks to the patient consent.
■ Certain imaging findings and patient characteristics could potentially assist radiologists and other physicians in identifying which joints are at risk for complications after IACS injections combined with local anesthetics.
■ The radiology community should actively engage in high-quality research to further understand these adverse joint findings and how they possibly relate to IACS injections to prevent or minimize complications.
Introduction
Osteoarthritis (OA) is among the most common joint diseases affecting the hip and knee, and the incidence is expected to increase with extended life expectancy and increasing obesity (1). Pain related to OA can be debilitating and can limit an individual’s activity and quality of life (2,3). Nonsurgical approaches, including pain control, are the recommended first-line treatments prior to considering joint replacement in patients with late-stage disease (4). However, many patients with OA are not suitable candidates for joint replacement because of their older age, comorbidities, or both.
Injection of intra-articular corticosteroids (IACSs), usually combined with local anesthetics, is commonly performed to treat pain related to hip and knee OA (5,6). The American College of Rheumatology conditionally recommends IACS injection to treat OA (7), while the Osteoarthritis Research Society International recommends that IACS injection should be considered, particularly in patients with moderate to severe pain whose response to oral analgesic or anti-inflammatory agents is not satisfactory, as well as in those with symptomatic knee OA with effusions or other physical signs of local inflammation (4). Unlike the American College of Rheumatology and Osteoarthritis Research Society International, the American Academy of Orthopedic Surgeons does not currently have recommendations for or against the use of IACS injection of the knee and advises that practitioners should be alert for emerging evidence that clarifies or helps determine the balance between benefits and potential harm. Patient preference should have a substantial influence on the type of treatment selected (8).
In 2015, Jüni et al performed a systematic meta-analysis on behalf of the Cochrane Musculoskeletal Group to determine the pain and quality of life associated with and the function and safety of IACS when compared with sham injection or no treatment in patients with knee OA (9). That meta-analysis comprised 27 trials that included 1767 participants. The overall quality of evidence was graded as low for all outcomes because treatment effect estimates were inconsistent, there was substantial variation across trials, and most trials had a high or unclear risk of bias. The authors concluded that IACS injections might have resulted in a moderate improvement in pain and a small improvement in physical function; however, the quality of the evidence was low, and the overall results were inconclusive. They also showed that IACS injections appeared to cause as many side effects as the placebo (13% vs 15%), but they emphasized that there was a lack of precise and reliable information about side effects and that only a small number of trials reported adverse joint events. The listed side effects after injection include arthralgia, joint swelling, back pain, and joint stiffness. Maricar et al (10) evaluated structural changes in the knee at MRI and radiography and the response to IACS injections. The authors demonstrated that more severe meniscal damage, greater joint space narrowing, and higher Kellgren-Lawrence grade were associated with a decreased likelihood of a long-term response (6 months). Additionally, baseline synovitis did not correlate with a treatment response.
Another review performed by Law et al focused on current concepts on the use of IACS injections for knee OA, including potential contraindications. The authors concluded that contraindications to IACS injections are all relative based on the best available evidence (11). Contraindications include active superficial skin or soft-tissue infection, suspected joint infection, unstable coagulopathy, anticoagulant therapy, uncontrolled diabetes mellitus, and broken skin at the injection site (11). Of note, anticoagulation treatment is not a general contraindication for IACS injection. Neither contraindications regarding pre-existing articular structural changes nor damage to the joint after IACS injections are mentioned in this review.
Despite the relative safety of IACS injections regarding systemic side effects, in a meta-analysis focusing on the effects of corticosteroids on human chondrocytes in vitro and animal articular cartilage in vivo, Wernecke et al reported that corticosteroids can have an adverse effect on cartilage, especially at higher doses (18–24 mg per cumulative dose) (12). The action by which corticosteroids are chondrotoxic is complex, but it seems to affect cartilage proteins (especially aggrecan, type II collagen, and proteoglycan) by mediating protein production and breakdown (13,14). McAlindon and colleagues compared IACS injections with placebo injections and found that IACS injections resulted in greater cartilage volume loss than did placebo injections (−0.21 mm vs −0.10 mm) but no significant difference in knee pain at 2 years (15). Zeng et al recently confirmed and extended these findings in a large subsample from the Osteoarthritis Initiative cohort, with 65 knees (21.7 per 100 person-years) showing worsening of radiographic OA in the IACS injection group compared with 90 knees (7.1 per 100 person-years) in the control group (16).
Local anesthetics, especially those with higher concentrations and longer exposures, have been associated with chondrolysis. Studies including animal evaluation (17), in vitro analysis (18), and local anesthetic infusion after glenohumeral arthroscopy (19) have demonstrated chondrotoxicity to varying degrees. While demonstrating time, concentration, and drug-dependent chondrotoxicity of local anesthetics on human chondrocytes, Breu et al also showed cellular death rates were higher in osteoarthritic cartilage than in intact cartilage (18).
Another recent retrospective observational study by Simeone et al focused on IACS injection in the hip and subsequent joint events in 70 patients. They reported that 44% of patients who received IACS injections showed radiographic progression of OA and 17% developed articular surface collapse (20). In addition, they found that patients who received IACS injections had significantly more adverse joint events than did a control group of patients without hip injections or a control group of patients who underwent shoulder injections. However, to our knowledge, there have been no large (>200 subjects) retrospective reviews or randomized controlled studies with long-term (≥1 year) follow-up.
Protocol for IACS Injections and Joint Findings
Our institution is a city hospital that provides care for underserved individuals. Many patients have multiple comorbidities that are frequently not well controlled and may be contraindications for surgery; thus, referrals for IACS injections to treat painful hip or knee OA are common. All IACS injections in the hip and knee joints are performed with US guidance by two musculoskeletal radiologists with 7 (A.J.K.) and 10 (A.M.M.) years of experience, and approximately 500 IACS injections are performed annually for the hip and knee joints combined. In 2018, we performed 459 IACS hip and knee injections (Table). Because many patients referred for IACS injection have primarily been seen by an orthopedic clinician, a recent radiograph of the target joint is usually available. A minority of patients also have undergone preprocedural MRI, which is a relatively common procedure at our institution. The IACS injections in hip and knee joints at our institution are composed of 40 mg of triamcinolone, 2 mL of 1% lidocaine, and 2 mL of 0.25% bupivacaine.
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Although the patients are not routinely called back for follow-up imaging at defined time points, some patients do return to the clinic after IACS injection, mainly because of insufficient pain relief or symptomatic worsening after an initial period of improvement, and they undergo additional imaging. Of the 459 patients who received an injection in 2018, 218 did not undergo radiographic or MRI follow-up or had total joint replacement without additional presurgical imaging. In addition to what has been reported by Simeone and colleagues (20) and others in the orthopedic and rheumatology literature (15,16), we have observed four main adverse joint findings in patients after IACS injections (Table): (a) accelerated OA progression (6%), (b) subchondral insufficiency fracture (0.9%), (c) complications of osteonecrosis (0.7%), and (d) rapid joint destruction, including bone loss (0.7%). Altogether, based on the available results of postprocedural imaging, we recorded 36 adverse joint events in 36 patients (19 women) out of a total of 459 IACS injections (8%). These patients were 37–79 years old (mean age, 57 years) and received one to three IACS injections (mean, 1.4 injections) with 2–15 months between the time of injection and imaging documentation of the joint event (mean time, 7 months). Most of the patients (72%) had preprocedural Kellgren-Lawrence (KL) moderate OA (KL grade 3) of the knee or hip (KL grade 0, n = 1; KL grade 2, n = 8; KL grade 3, n = 26; KL grade 4, n = 1).
In the following sections, we will detail these entities further, give an illustrative overview of case examples from our institution, provide an outlook on what this may mean for our clinical practice, and propose a potential radiologic research agenda on the topic.
Adverse Findings Observed after IACS Injection
Accelerated OA Progression
Rapid progressive OA (RPOA) or accelerated OA has been described by several authors (21–23). RPOA type 1 is synonymous with rapid loss of joint space on radiographs that is beyond the expected rate and was introduced in the context of clinical trials assessing the efficacy of nerve growth factor inhibitors, which are potent analgesics commonly administered as subcutaneous injections (24). Early trials of these nerve growth factor inhibitors have suggested that a minority of patients experience accelerated OA and require joint replacement earlier than expected (25). There is no clear definition of what exactly comprises RPOA type 1, but some authors have suggested that a joint space loss of more than 2 mm within a 12-month period represents accelerated joint space narrowing (24). The finding of joint space loss on radiographs commonly is a reflection of cartilage loss or meniscal tear and extrusion at MRI. However, when assessing interval joint space narrowing at radiography, minor variations in patient positioning have been shown to result in changes in joint space measurements without actual structural changes, and this needs to be considered when evaluating for interval changes (26). Associated findings of RPOA type 1, as detected with radiography, may include joint effusion, synovitis, adjacent soft-tissue changes, and subchondral bone changes, including extensive bone marrow edema and cystlike changes on the corresponding MRI (27) (Fig 1).
Figure 1a: Rapid progressive osteoarthritis joint space loss (type 1) in a 61-year-old woman who presented with hip pain. (a) Anteroposterior left hip radiograph shows joint space narrowing (arrowheads) and femoral and acetabular osteophytic changes (arrows) consistent with Kellgren-Lawrence grade III hip osteoarthritis. She was referred for US-guided steroid injection. (b) Four months after intraarticular corticosteroid injection, she presented with worsening left hip pain. Anteroposterior hip radiograph shows severe interval joint space narrowing (arrowheads) and enlarging subchondral cysts (arrows). (c) Coronal intermediate-weighted fat-suppressed MRI obtained at the same time as b shows complete loss of the acetabular and femoral cartilage (arrowheads), with subchondral cystic changes (black arrows). In addition, there is joint effusion and synovitis (*) and periarticular soft-tissue edema (white arrows). This patient underwent total joint replacement 3 months later.
Figure 1b: Rapid progressive osteoarthritis joint space loss (type 1) in a 61-year-old woman who presented with hip pain. (a) Anteroposterior left hip radiograph shows joint space narrowing (arrowheads) and femoral and acetabular osteophytic changes (arrows) consistent with Kellgren-Lawrence grade III hip osteoarthritis. She was referred for US-guided steroid injection. (b) Four months after intraarticular corticosteroid injection, she presented with worsening left hip pain. Anteroposterior hip radiograph shows severe interval joint space narrowing (arrowheads) and enlarging subchondral cysts (arrows). (c) Coronal intermediate-weighted fat-suppressed MRI obtained at the same time as b shows complete loss of the acetabular and femoral cartilage (arrowheads), with subchondral cystic changes (black arrows). In addition, there is joint effusion and synovitis (*) and periarticular soft-tissue edema (white arrows). This patient underwent total joint replacement 3 months later.
Figure 1c: Rapid progressive osteoarthritis joint space loss (type 1) in a 61-year-old woman who presented with hip pain. (a) Anteroposterior left hip radiograph shows joint space narrowing (arrowheads) and femoral and acetabular osteophytic changes (arrows) consistent with Kellgren-Lawrence grade III hip osteoarthritis. She was referred for US-guided steroid injection. (b) Four months after intraarticular corticosteroid injection, she presented with worsening left hip pain. Anteroposterior hip radiograph shows severe interval joint space narrowing (arrowheads) and enlarging subchondral cysts (arrows). (c) Coronal intermediate-weighted fat-suppressed MRI obtained at the same time as b shows complete loss of the acetabular and femoral cartilage (arrowheads), with subchondral cystic changes (black arrows). In addition, there is joint effusion and synovitis (*) and periarticular soft-tissue edema (white arrows). This patient underwent total joint replacement 3 months later.
Subchondral Insufficiency Fracture
Subchondral insufficiency fracture (SIF) of the knee and hip is becoming a more recognized abnormality in the orthopedic and radiology communities (28–30). Although SIF was once believed to occur predominantly in older patients and those with osteopenia, more recent studies have shown that younger adults who are active or who may have increased bone mineral density can also have SIF (28–30). Patients typically present with acute pain, which gradually worsens for weeks without an identifiable trauma (31). The SIF is typically found in a weight-bearing area, and there may be associated cartilage loss and meniscal tearing (32,33). If SIF is diagnosed early and does not show signs of articular collapse, it can heal with no change to the overlying articular surface (33,34). However, if SIF is not diagnosed at an early stage, it can progress to articular surface collapse, necessitating joint replacement (35). The radiographic appearance of SIF can be normal, unless there is collapse of the articular surface in advanced stages. Radiographic findings can range from subtle flattening of the articular surface to marked loss of sphericity with a fragmented articular surface (36). Frequently, SIF on radiographs is associated with accelerated joint space loss (37). What was commonly understood to be spontaneous osteonecrosis of the knee is now recognized as SIF without the potential to heal, leading to eventual collapse of the articular surface (38,39).
At MRI, subchondral hypointensity with varying thickness and extent is an early finding of SIF (28). There is a marked surrounding bone marrow edema pattern that is more intense than would be expected for typical OA (34). In the hip, SIF is usually associated with cartilage loss in the anterior or anteromedial weight-bearing region (40) (Fig 2). In the knee, SIF is often associated with meniscal tears with extrusion in the same compartment, particularly posterior root radial tears, with or without cartilage loss (32,41) (Fig 3). The most common anatomic location for SIF in the knee is the medial femoral condyle, and periarticular soft-tissue edema involving the posterior and medial soft tissues, including the medial collateral ligament, is consistently observed (42). Prognosis seems to be determined by extent and thickness of the subchondral hypointensity (34). Advanced SIF showing fluid dissecting below the subchondral plate is irreversible and will progress to articular surface collapse and secondary OA (40,43).
Figure 2a: Rapid progressive osteoarthritis joint space loss (type 1) and subchondral insufficiency fracture in a 53-year-old man who presented with hip pain. (a) Anteroposterior left hip radiograph shows mild osteophytic changes (arrows) and no joint space loss. This patient was referred for intra-articular corticosteroid injection. (b) Seven weeks after injection, he returned with worsening hip pain. Repeat anteroposterior left hip radiograph shows accelerated loss of joint space (arrows). (c) Sagittal intermediate-weighted fat-suppressed MRI obtained at the same time as b shows a linear subchondral hypointensity representing subchondral insufficiency fracture of the anterior superior femoral head with subtle flattening of the overlying articular surface (arrows). Extensive bone marrow edema extends to the femoral neck (*). (d) Corresponding coronal intermediate-weighted fat-suppressed MRI enables us to confirm the presence of a subchondral insufficiency fracture (arrow) and depicts the true extent of bone marrow edema (*).
Figure 2b: Rapid progressive osteoarthritis joint space loss (type 1) and subchondral insufficiency fracture in a 53-year-old man who presented with hip pain. (a) Anteroposterior left hip radiograph shows mild osteophytic changes (arrows) and no joint space loss. This patient was referred for intra-articular corticosteroid injection. (b) Seven weeks after injection, he returned with worsening hip pain. Repeat anteroposterior left hip radiograph shows accelerated loss of joint space (arrows). (c) Sagittal intermediate-weighted fat-suppressed MRI obtained at the same time as b shows a linear subchondral hypointensity representing subchondral insufficiency fracture of the anterior superior femoral head with subtle flattening of the overlying articular surface (arrows). Extensive bone marrow edema extends to the femoral neck (*). (d) Corresponding coronal intermediate-weighted fat-suppressed MRI enables us to confirm the presence of a subchondral insufficiency fracture (arrow) and depicts the true extent of bone marrow edema (*).
Figure 2c: Rapid progressive osteoarthritis joint space loss (type 1) and subchondral insufficiency fracture in a 53-year-old man who presented with hip pain. (a) Anteroposterior left hip radiograph shows mild osteophytic changes (arrows) and no joint space loss. This patient was referred for intra-articular corticosteroid injection. (b) Seven weeks after injection, he returned with worsening hip pain. Repeat anteroposterior left hip radiograph shows accelerated loss of joint space (arrows). (c) Sagittal intermediate-weighted fat-suppressed MRI obtained at the same time as b shows a linear subchondral hypointensity representing subchondral insufficiency fracture of the anterior superior femoral head with subtle flattening of the overlying articular surface (arrows). Extensive bone marrow edema extends to the femoral neck (*). (d) Corresponding coronal intermediate-weighted fat-suppressed MRI enables us to confirm the presence of a subchondral insufficiency fracture (arrow) and depicts the true extent of bone marrow edema (*).
Figure 2d: Rapid progressive osteoarthritis joint space loss (type 1) and subchondral insufficiency fracture in a 53-year-old man who presented with hip pain. (a) Anteroposterior left hip radiograph shows mild osteophytic changes (arrows) and no joint space loss. This patient was referred for intra-articular corticosteroid injection. (b) Seven weeks after injection, he returned with worsening hip pain. Repeat anteroposterior left hip radiograph shows accelerated loss of joint space (arrows). (c) Sagittal intermediate-weighted fat-suppressed MRI obtained at the same time as b shows a linear subchondral hypointensity representing subchondral insufficiency fracture of the anterior superior femoral head with subtle flattening of the overlying articular surface (arrows). Extensive bone marrow edema extends to the femoral neck (*). (d) Corresponding coronal intermediate-weighted fat-suppressed MRI enables us to confirm the presence of a subchondral insufficiency fracture (arrow) and depicts the true extent of bone marrow edema (*).
Figure 3a: Subchondral insufficiency fracture in a 69-year-old woman who presented with acutely worsening knee pain without known trauma. (a) Anteroposterior radiograph of the right knee shows possible medial compartment joint space narrowing (arrows) without osteophytes. There are no signs of osteonecrosis or subchondral insufficiency fracture. (b) Coronal intermediate-weighted fat-suppressed MRI obtained at the same time as a shows a subchondral insufficiency fracture of the medial femoral condyle, without collapse of the articular surface (arrow). In addition, there is marked femoral and tibial bone marrow edema (*). This patient was not treated with conservative measures (ie, switch to non–weight-bearing activity) and received an intra-articular corticosteroid injection. (c) Eleven months later, she returned with continued right knee pain. Repeat anteroposterior radiograph of the right knee shows collapse of the medial femoral condyle articular surface (arrows). (d) Coronal intermediate-weighted MRI acquired at the same time as c demonstrates deformity of the articular surface (short arrow) of the medial femoral condyle in the area of a previously noted subchondral insufficiency fracture (long arrow). In addition, there is marked bone marrow edema (*).
Figure 3b: Subchondral insufficiency fracture in a 69-year-old woman who presented with acutely worsening knee pain without known trauma. (a) Anteroposterior radiograph of the right knee shows possible medial compartment joint space narrowing (arrows) without osteophytes. There are no signs of osteonecrosis or subchondral insufficiency fracture. (b) Coronal intermediate-weighted fat-suppressed MRI obtained at the same time as a shows a subchondral insufficiency fracture of the medial femoral condyle, without collapse of the articular surface (arrow). In addition, there is marked femoral and tibial bone marrow edema (*). This patient was not treated with conservative measures (ie, switch to non–weight-bearing activity) and received an intra-articular corticosteroid injection. (c) Eleven months later, she returned with continued right knee pain. Repeat anteroposterior radiograph of the right knee shows collapse of the medial femoral condyle articular surface (arrows). (d) Coronal intermediate-weighted MRI acquired at the same time as c demonstrates deformity of the articular surface (short arrow) of the medial femoral condyle in the area of a previously noted subchondral insufficiency fracture (long arrow). In addition, there is marked bone marrow edema (*).
Figure 3c: Subchondral insufficiency fracture in a 69-year-old woman who presented with acutely worsening knee pain without known trauma. (a) Anteroposterior radiograph of the right knee shows possible medial compartment joint space narrowing (arrows) without osteophytes. There are no signs of osteonecrosis or subchondral insufficiency fracture. (b) Coronal intermediate-weighted fat-suppressed MRI obtained at the same time as a shows a subchondral insufficiency fracture of the medial femoral condyle, without collapse of the articular surface (arrow). In addition, there is marked femoral and tibial bone marrow edema (*). This patient was not treated with conservative measures (ie, switch to non–weight-bearing activity) and received an intra-articular corticosteroid injection. (c) Eleven months later, she returned with continued right knee pain. Repeat anteroposterior radiograph of the right knee shows collapse of the medial femoral condyle articular surface (arrows). (d) Coronal intermediate-weighted MRI acquired at the same time as c demonstrates deformity of the articular surface (short arrow) of the medial femoral condyle in the area of a previously noted subchondral insufficiency fracture (long arrow). In addition, there is marked bone marrow edema (*).
Figure 3d: Subchondral insufficiency fracture in a 69-year-old woman who presented with acutely worsening knee pain without known trauma. (a) Anteroposterior radiograph of the right knee shows possible medial compartment joint space narrowing (arrows) without osteophytes. There are no signs of osteonecrosis or subchondral insufficiency fracture. (b) Coronal intermediate-weighted fat-suppressed MRI obtained at the same time as a shows a subchondral insufficiency fracture of the medial femoral condyle, without collapse of the articular surface (arrow). In addition, there is marked femoral and tibial bone marrow edema (*). This patient was not treated with conservative measures (ie, switch to non–weight-bearing activity) and received an intra-articular corticosteroid injection. (c) Eleven months later, she returned with continued right knee pain. Repeat anteroposterior radiograph of the right knee shows collapse of the medial femoral condyle articular surface (arrows). (d) Coronal intermediate-weighted MRI acquired at the same time as c demonstrates deformity of the articular surface (short arrow) of the medial femoral condyle in the area of a previously noted subchondral insufficiency fracture (long arrow). In addition, there is marked bone marrow edema (*).
Complications of Osteonecrosis
Osteonecrosis is a frequently encountered disease, most often occurring in the femoral head and condyles (44). Osteonecrosis without collapse of the articular surface is often radiographically occult, and MRI is needed for diagnosis (45). Patients can present with an insidious onset of pain and can be asymptomatic until the development of insufficiency fractures or articular surface collapse (46). Pain symptoms and treatment plans are related to the possibility or presence of subchondral bone plate collapse. At MRI, the size of the area of osteonecrosis and the associated bone marrow edema pattern are predictors of collapse (47). Collapse results in the development of secondary OA and persistent pain, and treatment options at this stage are limited to joint replacement. Patients with painful noncollapsed osteonecrosis of the femoral heads are often referred for IACS treatment (Fig 4). To our knowledge, there are no standardized treatment guidelines for these patients, and there is no recognized contraindication or benefit to these patients receiving an IACS (48).
Figure 4a: Osteonecrosis in a 29-year-old man who presented with right hip pain. (a) Anteroposterior radiograph of the pelvis shows osteonecrosis in the right femoral head, with preserved femoral head contours (arrows). He subsequently went to the sports medicine clinic and received a right hip joint corticosteroid injection for pain. (b) Three months later, he was referred to our institution for repeat intra-articular corticosteroid injection. The patient presented with a severe limp when walking and described the pain as worse than his original pain. Preprocedural sagittal US image shows a defect in the anterior right femoral head cortex (black arrow) and moderate joint effusion with a severely thickened anterior joint capsule (white arrows). The intra-articular corticosteroid injection was cancelled given the US findings, and the referring orthopedic physician was informed of the findings. (c) Repeat anteroposterior right hip radiograph obtained 1 week after US when the patient was seen in the orthopedic clinic for a follow-up visit enabled confirmation that the superior femoral head articular surface had collapsed (arrows), and the patient underwent right hip joint replacement.
Figure 4b: Osteonecrosis in a 29-year-old man who presented with right hip pain. (a) Anteroposterior radiograph of the pelvis shows osteonecrosis in the right femoral head, with preserved femoral head contours (arrows). He subsequently went to the sports medicine clinic and received a right hip joint corticosteroid injection for pain. (b) Three months later, he was referred to our institution for repeat intra-articular corticosteroid injection. The patient presented with a severe limp when walking and described the pain as worse than his original pain. Preprocedural sagittal US image shows a defect in the anterior right femoral head cortex (black arrow) and moderate joint effusion with a severely thickened anterior joint capsule (white arrows). The intra-articular corticosteroid injection was cancelled given the US findings, and the referring orthopedic physician was informed of the findings. (c) Repeat anteroposterior right hip radiograph obtained 1 week after US when the patient was seen in the orthopedic clinic for a follow-up visit enabled confirmation that the superior femoral head articular surface had collapsed (arrows), and the patient underwent right hip joint replacement.
Figure 4c: Osteonecrosis in a 29-year-old man who presented with right hip pain. (a) Anteroposterior radiograph of the pelvis shows osteonecrosis in the right femoral head, with preserved femoral head contours (arrows). He subsequently went to the sports medicine clinic and received a right hip joint corticosteroid injection for pain. (b) Three months later, he was referred to our institution for repeat intra-articular corticosteroid injection. The patient presented with a severe limp when walking and described the pain as worse than his original pain. Preprocedural sagittal US image shows a defect in the anterior right femoral head cortex (black arrow) and moderate joint effusion with a severely thickened anterior joint capsule (white arrows). The intra-articular corticosteroid injection was cancelled given the US findings, and the referring orthopedic physician was informed of the findings. (c) Repeat anteroposterior right hip radiograph obtained 1 week after US when the patient was seen in the orthopedic clinic for a follow-up visit enabled confirmation that the superior femoral head articular surface had collapsed (arrows), and the patient underwent right hip joint replacement.
Rapid Joint Destruction Including Bone Loss
RPOA type 2 is another term established in the context of clinical trials of nerve growth factor inhibitors and is defined as rapid articular destruction with accelerated bone loss not typically seen in patients with OA (49). Several case reports have described the potential cause of RPOA type 2, although there is a lack of larger studies given the relatively low prevalence of this disease (50). Initial reports attributed this entity to accelerated osteonecrosis, while others have suggested this is advanced joint destruction related to undiagnosed SIF (51,52). Although we have seen RPOA type 2 in patients receiving IACS injections (Fig 5), it has also been found to randomly occur in patients without prior intervention or underlying disease (53).
Figure 5a: Rapid progressive osteoarthritis (RPOA) type 2 in an 81-year-old woman with right hip pain who was referred for right hip intra-articular corticosteroid injection. (a) Anteroposterior right hip radiograph shows no definite osteoarthritis. (b) Within 3 months after receiving the injection, this patient presented with worsening right hip pain. Repeat anteroposterior right hip radiograph shows subchondral insufficiency fracture, with collapse of the superior femoral head articular surface (arrows). (c) Pain increased markedly over the following month, and this repeat anteroposterior right hip radiograph shows bone loss and destruction of the femoral head with severe joint space loss, consistent with RPOA type 2 (arrows). In addition, there are extensive cystic changes at the acetabulum (arrowheads).
Figure 5b: Rapid progressive osteoarthritis (RPOA) type 2 in an 81-year-old woman with right hip pain who was referred for right hip intra-articular corticosteroid injection. (a) Anteroposterior right hip radiograph shows no definite osteoarthritis. (b) Within 3 months after receiving the injection, this patient presented with worsening right hip pain. Repeat anteroposterior right hip radiograph shows subchondral insufficiency fracture, with collapse of the superior femoral head articular surface (arrows). (c) Pain increased markedly over the following month, and this repeat anteroposterior right hip radiograph shows bone loss and destruction of the femoral head with severe joint space loss, consistent with RPOA type 2 (arrows). In addition, there are extensive cystic changes at the acetabulum (arrowheads).
Figure 5c: Rapid progressive osteoarthritis (RPOA) type 2 in an 81-year-old woman with right hip pain who was referred for right hip intra-articular corticosteroid injection. (a) Anteroposterior right hip radiograph shows no definite osteoarthritis. (b) Within 3 months after receiving the injection, this patient presented with worsening right hip pain. Repeat anteroposterior right hip radiograph shows subchondral insufficiency fracture, with collapse of the superior femoral head articular surface (arrows). (c) Pain increased markedly over the following month, and this repeat anteroposterior right hip radiograph shows bone loss and destruction of the femoral head with severe joint space loss, consistent with RPOA type 2 (arrows). In addition, there are extensive cystic changes at the acetabulum (arrowheads).
Figures 1–5 are typical examples of these disease entities recently identified in our clinical practice. All patients had undergone IACS injection. We acknowledge that we do not have insight into whether these observed events were already ongoing at the time of injection or if these findings are an actual result or complication of the IACS injection itself.
Outlook
IACS injections are frequently performed for pain relief in patients with knee or hip OA. Recent reports and case series have suggested that certain preexisting conditions (older age, white race) may increase the risk for a negative joint outcome after IACS injection (54,55). Currently, to our knowledge, there is no recommendation for imaging before an IACS injection to detect such entities prior to the intervention. Subchondral insufficiency fracture and osteonecrosis can sometimes be diagnosed by using radiography, although the findings can be subtle or radiographically occult. However, given the relative ease of performance and the low cost of radiography, there should be a low threshold to obtain radiographs before performing an IACS injection, as the intervention may affect the disease course (ie, it may result in accelerated progression).
Identification of a subchondral insufficiency fracture before IACS injection is clinically important, as glucocorticoids may inhibit the healing process of such a fracture (56). The primary treatment of a subchondral insufficiency fracture is conservative, including protected weight-bearing or non–weight-bearing activities, and some authors have proposed the supportive use of bisphosphonates or prostacyclin analogs (57,58). There is little evidence regarding these supportive approaches, however, given the small number of treated patients and the potential underdiagnosis of subchondral insufficiency fracture due to lack of radiologic awareness. Performance of IACS injection in the presence of a subchondral insufficiency fracture could result in decreased joint pain, potentially leading to increased weight bearing and possible acceleration of subchondral insufficiency fracture to joint collapse. Additionally, if IACS injection is performed with US guidance, findings suggestive of an inflammatory process on preinjection US images, including a larger-than-expected joint effusion, extensive intraarticular debris, or synovial thickening and medial soft-tissue thickening with vascularity on Doppler US images, could indicate an on-going active joint process, including a radiographically occult subchondral insufficiency fracture, and may lead physicians to not perform the injection at that time but rather perform MRI prior to IACS injection.
In patients with no OA or only mild OA on a radiograph who are referred for IACS injection to treat joint pain, the indication for IACS injection should be closely scrutinized. Case series and retrospective reviews have shown that some patients who develop rapid progressive joint space loss or destructive OA tend to have no OA or only mild OA at initial presentation (50). Clinicians should consider obtaining a repeat radiograph before each subsequent IACS injection to evaluate for progressive narrowing of the joint space and any interval changes in the articular surface that can indicate subchondral insufficiency fracture or type 1 or 2 RPOA.
To our knowledge, overviews regarding the treatment of osteonecrosis do not discuss IACS injection to treat pain (59). Orthopedists do not have a contraindication for performing IACS injections in patients with osteonecrosis. Patients with already collapsed osteonecrosis could be candidates for IACS injection, given that joint replacement would be their only other treatment option to relieve pain. Controversy arises when patients with a diagnosis of femoral head osteonecrosis are referred for IACS injection and have preserved femoral head contours. When a patient with femoral head osteonecrosis without collapse is referred to our clinic for IACS injection, the potential of accelerating the osteonecrosis leading to joint collapse, the potential for worsened pain, and the need for joint replacement to relieve the pain are now routinely included in the patient’s informed consent at our institution.
In conclusion, intra-articular corticosteroid (IACS) injections are frequently performed with the hope of relieving joint pain. However, large retrospective analyses and prospective studies evaluating accelerated osteoarthritis (OA) or joint destruction after IACS injections are lacking. We believe that certain patient characteristics, including but not limited to acute change in pain not explained by using radiography and no or only mild OA at radiography, should lead to careful reconsideration of a planned IACS injection. In these circumstances, MRI may be helpful to further evaluate the actual cause of pain prior to a planned injection. Given that IACS injections are increasingly performed to treat pain in patients with hip or knee OA, we suggest that the radiologic community should actively engage in high-quality research on this topic to better understand potential at-risk conditions prior to intervention and to better understand potential adverse joint events after these procedures to avoid possible complications.
Disclosures of Conflicts of Interest: A.J.K. disclosed no relevant relationships. F.W.R. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a Boston Imaging Core Lab shareholder. Other relationships: disclosed no relevant relationships. A.M.M. disclosed no relevant relationships. L.E.D. disclosed no relevant relationships. M.D.C. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a Boston Imaging Core Lab shareholder. Other relationships: disclosed no relevant relationships. A.G. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a consultant for TissueGene, MerckSerono, Pfizer, AstraZeneca, Galapagos, and Roche; is a Boston Imaging Core Lab shareholder. Other relationships: disclosed no relevant relationships.Author Contributions
Author contributions: Guarantors of integrity of entire study, A.J.K., A.M.M., A.G.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors; literature research, all authors; clinical studies, A.M.M., A.G.; experimental studies, A.M.M.; statistical analysis, A.M.M.; and manuscript editing, all authors
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Article History
Received: Feb 13 2019Revision requested: Apr 12 2019
Revision received: Aug 8 2019
Accepted: Aug 21 2019
Published online: Oct 15 2019
Published in print: Dec 2019
